Rates of women who are opting for preventive mastectomies, such as Angeline Jolie, have increased by an estimated 50 percent in recent years, experts say. But many doctors are puzzled because the operation doesn't carry a 100 percent guarantee, it's major surgery -- and women have other options, from a once-a-day pill to careful monitoring.

Risk of miscarriage more than doubled in women who took non-steroidal anti-inflammatory drugs, or NSAIDs, during the first 20 weeks of gestation, according to researchers who scrutinized health records from nearly 50,000 Canadian women.

The study appears in the latest issue of the Canadian Medical Association Journal.

“I would strongly suggest that women take no non-steroidal anti-inflammatory drugs during the first trimester,” said study co-author Anick Berard, a professor of epidemiology at the University of Montreal and director of the research unit on medications and pregnancy at Centre Hospitalier Universitaire Ste. Justine."If a woman is taking an NSAID for a chronic condition she really has to talk to her health care provider to see if it's feasible to stop at least during the first trimester."

Use of NSAIDs is fairly common, Berard noted, adding that studies have shown that up to 17 percent of pregnant women take the drugs, either in prescription or over-the-counter formulations. The new study investigated use of non-aspirin NSAIDs such as ibuprofen, naproxen and other drugs.

However, a leading expert in maternal fetal medicine cautioned women not to overreact to the new findings. The increased risk could be due to something else that women who took NSAIDS had in common, said Dr. Hyagriv Simhan, associate professor and chief of the division of maternal-fetal medicine at the University of Pittsburgh Medical Center and medical director of obstetrical services at Magee-Womens Hospital of UPMC.

Don't overreact, expert says
“I wouldn’t want this to be a reason for women who have taken a Motrin before they realized they were pregnant to freak out,” Simhan said.

Beyond this, Simhan said, there are legitimate reasons for women to be taking NSAIDS. “This study wouldn’t necessarily make me change the way I practice,” he added.

The Canadian study compared the medical records of 4,705 women who had a miscarriage during the first 20 weeks of gestation with records of 47,050 women who became pregnant and delivered a child. The women in the study were aged 15 to 45 when they became pregnant.

Berard and her colleagues considered a woman to have been exposed to an NSAID if she had a prescription for the drug filled before she became pregnant or during early pregnancy. Most NSAIDs in Canada are available through prescription rather than over-the-counter, the authors said.

Among women who had miscarriages, 352 had taken NSAIDs, compared with 1,213 of the women who did not experience pregnancy loss.

When calculating the risk associated with NSAID use, the researchers accounted for other factors that might increase the likelihood of miscarriage, such as diabetes, high blood pressure, heart disease, asthma, lupus, rheumatoid arthritis, depression and anxiety.

Taking all those factors into account, Berard and her colleagues determined that women who took prescription NSAIDs early in pregnancy were 2.4 times as likely to have a miscarriage as those who did not. The rate of miscarriage in women who took NSAIDs was about 35 percent, compared with the normal rate of miscarriage, which is about 15 percent.

While the study didn't address the kind of over-the-counter use of NSAIDs found in the U.S., the authors cautioned against any use of the drugs in early pregnancy.

"Gestational exposure to any type or dosage of non-aspirin NSAIDs may increase risk of spontaneous abortion. These drugs should be used with caution during pregnancy," the authors concluded.

NSAIDs may affect prostaglandin levels
The researchers hypothesize that NSAIDs could have an impact on pregnancy because the drugs affect the levels of hormone-like substances known as prostaglandins. Normally in pregnancy, prostaglandins decrease in the uterus in a consistent way, Berard said. It’s possible that NSAIDs cause these levels to fluctuate, she suggested.

One thing Berard and her colleagues don’t know was why the women were given prescriptions for NSAIDs. That’s an important factor, Simhan said. It’s always possible that some of the women who miscarried were taking the medications for cramping which is a sign of impending pregnancy loss, he added.

Berard doesn’t believe this is the case. Women who had miscarriages generally didn’t get more prescriptions for NSAIDs in the two weeks leading up to their pregnancy losses, she explained.

Previous studies about the impact of NSAIDs in early pregnancy had shown mixed results, Berard said.

Nevertheless, she does allow that this kind of study can’t prove that NSAIDs actually cause pregnancy loss.

“We cannot say for 100 percent sure that this is a true drug effect,” she said. “But we’re one step closer to proving causality when there is repetition of the finding. And there is at least one other study looking at this specifically that found an increased risk.”

Linda Carroll is a health and science writer living in New Jersey. Her work has appeared in The New York Times, Newsday, Health magazine and SmartMoney. She is co-author of the new book "The Concussion Crisis: Anatomy of a Silent Epidemic."

Video: Use of NSAIDs could double risk of miscarriage

Closed captioning of: Use of NSAIDs could double risk of miscarriage

>>>pregnant or trying to conceive. it involves the risk of miscarriage. still in many ways a medical mystery. while the experts keep trying to learn more about what causes miscarriages, and how to prevent them, a new study of 47,000 women has found one more piece of the puzzle that women may want to consider. and it involves some big
brand namepain relievers
that are in so many of our homes in this country. the story tonight from our chief science correspondent,
robert bazell
.

>> reporter: like most
pregnant women
,ester worries about anything that could harm her unborn child.

>>i always check with my doctor before needing to take any particular medication.

>> reporter: experts say the study out today reinforces what a good idea that is. some of the most popular over-the-counter
pain relievers
, so-called nsaids could be cause for concern early in pregnancy including ibuprofen sold under names like motrin and advil and naproxyn sold as aleve. they carry warnings against use late in pregnancy. but the study out today from the team of
university of montreal
, shows that taken early in pregnancy occurring the first 20 weeks, the drugs made more than double the risk of miscarriage. researchers say acetaminophen sold at tylenol does not seem to be a problem.

>>the studies that we do in
pregnant women
are certainly not to alarm women. it's to give more information to help women and prescribers physician, to gain better knowledge of what's happening with medication used in pregnancies.

>> reporter: experts not involved with the research agree.

>>i think this is an important study. it's confirmatory. there have been other evidence that there are some concerns with these kinds of drugs.

>> reporter: because the effect from the drugs can occur so early in pregnancy, experts, even the drug makers, advise women start talking with their doctors about any medications they are taking as soon as they blap to get pregnant. miscarriages are common but while their cause is often unknown, information like this latest study can helpester and other perspective mothers make the best decisions.
robert bazell
, nbc news, new york.